A 5-year renewal of the Center for Environmental Genetics (CEG) is proposed. The unifying research focus of the Center is to study the impact of genetic diversity on individual susceptibility to toxic environmental agents. The CEG has a long history (10 years) and broad range of accomplishments in environmental genetics, and this research focus has become increasingly important in environmental health science research. The Specific Aims are: Aim 1. Facilitate the identification of susceptibility genes that may interact with environmental agents to induce complex diseases such as type II diabetes, asthma, intracranial strokes, hypertension, and lung cancer. Aim 2. Facilitate studies to analyze the impact of genetic variants of known genes on individual response to specific environmental agents such as airborne particulates, environmental estrogens, metals, and ionizing radiation. Aim 3. Facilitate studies to examine signal transduction pathways induced by response to environmental agents whose exposure is associated with a disease or tissue/cellular damage. Aim 4. Encourage investigators to direct their research toward a focus in environmental genetics. Aim 5. Develop a partnership with the surrounding community to provide education, awareness of environmental health issues, and public policies through the Community Outreach and Education Program (COEP) Core. We have four highly successful Research Cores that have been in existence for at least 5 year, Ecogenetics, Genetic Toxicology, Respiratory Toxicology, and Signal Transduction. The Human Populations Research Core was initiated to reflect our emphasis to perform human studies related to our research focus. In this renewal application, we will respond to new advances in genomics, proteomics and bioinformatics, and genetic epidemiology by modifying the Facilities and Services Cores to offer the following services to CEG members: 1) Bioinformatic data analysis procedures, 2) Microarray expression and protein analysis methodology, and 3) Procedures for conducting human populations studies. The goal of the Center is to understand and thus, either prevent or intervene in complex human disease by determining the role of gene- environment interaction in the development of diseases.